tbuckley/cabot-search huggingface dataset:
3D‐Printed Radiopaque Microdevices with Enhanced Mucoadhesive Geometry for Oral Drug Delivery
Authors: Tien‐Jen Chang, Rolf Bech Kjeldsen, Juliane Fjelrad Christfort, Eduard Marzo Vila, Tommy Sonne Alstrøm, Kinga Zór, En‐Te Hwu, Line Hagner Nielsen, Anja Boisen
Journal: Advanced Healthcare Materials (2022)

During the past decades, microdevices have been evaluated as a means to overcome challenges within oral drug delivery, thus improving bioavailability. Fabrication of microdevices is often limited to planar or simple 3D designs. Therefore, this work explores how microscale stereolithography 3D printing can be used to fabricate radiopaque microcontainers with enhanced mucoadhesive geometries, which can enhance bioavailability by increasing gastrointestinal retention. Ex vivo force measurements suggest increased mucoadhesion of microcontainers with adhering features, such as pillars and arrows, compared to a neutral design. In vivo studies, utilizing planar X-ray imaging, show the time-dependent gastrointestinal location of microcontainers, whereas computed tomography scanning and cryogenic scanning electron microscopy reveal information about their spatial dynamics and mucosal interactions, respectively. For the first time, the effect of 3D microdevice modifications on gastrointestinal retention is traced in vivo, and the applied methods provide a much-needed approach for investigating the impact of device design on gastrointestinal retention.
Noninvasive serum biomarkers for liver fibrosis in NAFLD: current and future
Authors: Tina Reinson, Ryan M. Buchanan, Christopher D. Byrne
Journal: Clinical and Molecular Hepatology (2022)

In the last 20 years, noninvasive serum biomarkers to identify liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) have been developed, validated against liver biopsy (the gold standard for determining the presence of liver fibrosis) and made available for clinicians to use to identify ≥F3 liver fibrosis. The aim of this review is firstly to focus on the current use of widely available biomarkers and their performance for identifying ≥F3. Secondly, we discuss whether noninvasive biomarkers have a role in identifying F2, a stage of fibrosis that is now known to be a risk factor for cirrhosis and overall mortality. We also consider whether machine learning algorithms offer a better alternative for identifying individuals with ≥F2 fibrosis. Thirdly, we summarise the utility of noninvasive serum biomarkers for predicting liver related outcomes (e.g., ascites and hepatocellular carcinoma) and non-liver related outcomes (e.g., cardiovascular-related mortality and extra hepatic cancers). Finally, we examine whether serial measurement of biomarkers can be used to monitor liver disease, and whether the use of noninvasive biomarkers in drug trials for non-alcoholic steatohepatitis can accurately, compared to liver histology, monitor liver fibrosis progression/regression. We conclude by offering our perspective on the future of serum biomarkers for the detection and monitoring of liver fibrosis in NAFLD.
Causes and risk profiles of mortality among individuals with nonalcoholic fatty liver disease
Authors: Peter Konyn, Aijaz Ahmed, Donghee Kim
Journal: Clinical and Molecular Hepatology (2022)

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and worldwide. Though nonalcoholic fatty liver per se may not be independently associated with an increased risk for all-cause mortality, it is associated with a number of harmful metabolic risk factors, such as type 2 diabetes mellitus, hyperlipidemia, obesity, a sedentary lifestyle, and an unhealthy diet. The fibrosis stage is a predictor of all-cause mortality in NAFLD. Mortality in individuals with NAFLD has been steadily increasing, and the most common cause-specific mortality for NAFLD is cardiovascular disease, followed by extra-hepatic cancer, liver-related mortality, and diabetes. High-risk profiles for mortality in NAFLD include PNPLA3 I148M polymorphism, low thyroid function and hypothyroidism, and sarcopenia. Achieving weight loss through adherence to a high-quality diet and sufficient physical activity is the most important predictor of improvement in NAFLD severity and the benefit of survival. Given the increasing health burden of NAFLD, future studies with more long-term mortality data may demonstrate an independent association between NAFLD and mortality.
Levothyroxine: Conventional and Novel Drug Delivery Formulations
Authors: Hanqing Liu, Wei Li, Wen Zhang, Shengrong Sun, Chuang Chen
Journal: Endocrine Reviews (2022)

Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.
Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function
Authors: Yuanyue Zhang, Jacob T. Bailey, En Xu, Kunal Singh, Marieke Lavaert, Verena M. Link, Shanti D’Souza, Alex Hafiz, Jian Cao, Gaoyuan Cao, Derek B. Sant’Angelo, Wei Sun, Yasmine Belkaid, Avinash Bhandoola, Dorian B. McGavern, Qi Yang
Journal: Nature Immunology (2022)
Protective effects of alpha-mangostin encapsulated in cyclodextrin-nanoparticle on cerebral ischemia
Authors: Natsumi Oka, Van Thi Hong Doan, Hirofumi Matsubara, Takahiko Imai, Yukie Yoshioka, Jun Katsuki, Shota Fujii, Shinsuke Nakamura, Masamitsu Shimazawa, Hideaki Hara, Kazuo Sakurai
Journal: Journal of Controlled Release (2022)
Climate emergency: The polluters must pay
Authors: Frances MacGuire
Journal: BMJ (2022)

The UN's annual climate summit, COP27, held this year in Egypt, has as its ultimate objective to avoid dangerous climate change-the greatest threat to health in the 21st century. 1 Public health clinicians are used to arguing the case for investing in the prevention of ill health while promoting good health, a clarion call which frequently falls on deaf ears despite the staggering savings that could be achieved in health budgets and avoided health harms.After 30 years of international negotiations, greenhouse gas emissions continue to rise inexorably, and the predicted impacts are being felt around the world as floods, wildfires, drought, and heatwaves bring devastating impacts to human health, lives, and livelihoods.Public health has a clear role in highlighting the costs of the impact of climate change and benefits of taking action through well established metrics such as human health in years of life lost, disability adjusted life years, and quality adjusted life years.
<scp>GALTectomy</scp> increases the risk of allergic rhinitis: A nationwide population‐based cohort study
Authors: Tzu‐Min Lin, Hui‐Ching Hsu, Yu‐Chuan Shen, Yu‐Sheng Chang, Wei‐Sheng Chen, Hsiang‐Yen Lee, Ching‐Kuei Chang, Tzu‐Tung Kuo, Shu‐Chuan Chen, Jin‐Hua Chen, Chi‐Ching Chang
Journal: Allergy (2022)
Risk of Anaplastic Large Cell Lymphoma Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Ductal Carcinoma in Situ
Authors: Connor J. Kinslow, David M. DeStephano, Christine H. Rohde, Lisa A. Kachnic, Simon K. Cheng, Alfred I. Neugut, David P. Horowitz
Journal: JAMA Network Open (2022)

This cohort study examines the risk of anaplastic large cell lymphoma (ALCL) following postmastectomy implant reconstruction among US women with breast cancer and ductal carcinoma in situ (DCIS).
Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition
Authors: Cara Abecunas, Christopher E. Whitehead, Elizabeth K. Ziemke, Douglas G. Baumann, Christy L. Frankowski-McGregor, Judith S. Sebolt-Leopold, Mohammad Fallahi-Sichani
Journal: Cancer Research (2022)

Abstract Neurofibromin 1 (NF1) loss of function (LoF) mutations are frequent in melanoma and drive hyperactivated RAS and tumor growth. NF1LoF melanoma cells, however, do not show consistent sensitivity to individual MEK, ERK, or PI3K/mTOR inhibitors. To identify more effective therapeutic strategies for treating NF1LoF melanoma, we performed a targeted kinase inhibitor screen. A tool compound named MTX-216 was highly effective in blocking NF1LoF melanoma growth in vitro and in vivo. Single-cell analysis indicated that drug-induced cytotoxicity was linked to effective cosuppression of proliferation marker Ki-67 and ribosomal protein S6 phosphorylation. The antitumor efficacy of MTX-216 was dependent on its ability to inhibit not only PI3K, its nominal target, but also SYK. MTX-216 suppressed expression of a group of genes that regulate mitochondrial electron transport chain and are associated with poor survival in patients with NF1LoF melanoma. Furthermore, combinations of inhibitors targeting either MEK or PI3K/mTOR with an independent SYK kinase inhibitor or SYK knockdown reduced the growth of NF1LoF melanoma cells. These studies provide a path to exploit SYK dependency to selectively target NF1LoF melanoma cells. Significance: A kinase inhibitor screen identifies SYK as a targetable vulnerability in melanoma cells with NF1 loss of function.
Reported Awareness and Adoption of 2021 Estimated Glomerular Filtration Rate Equations Among US Clinical Laboratories, March 2022
Authors: Jonathan R. Genzen, Rhona J. Souers, Lauren N. Pearson, David M. Manthei, Allison B. Chambliss, Zahra Shajani-Yi, W. Greg Miller
Journal: JAMA (2022)

This study includes clinical laboratories that participated in the first general chemistry proficiency testing survey in 2022 to assess awareness and adoption of new equations from the Chronic Kidney Disease Epidemiology Collaboration for estimated glomerular filtration rate (eGFR) that eliminated race-adjustment factors, including one based on creatinine and one based on creatinine and cystatin C.
Fluid Bolus Administration and Cardiovascular Collapse in Critically Ill Patients Undergoing Tracheal Intubation
Authors: Ambika Tejpal, Matteo Parotto, Michael C. Sklar
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Aberrant L-Fucose Accumulation and Increased Core Fucosylation Are Metabolic Liabilities in Mesenchymal Glioblastoma
Authors: Valentina Pieri, Alberto L. Gallotti, Denise Drago, Manuela Cominelli, Ilaria Pagano, Valentina Conti, Silvia Valtorta, Angela Coliva, Sara Lago, Daniela Michelatti, Luca Massimino, Federica Ungaro, Laura Perani, Antonello Spinelli, Antonella Castellano, Andrea Falini, Alessio Zippo, Pietro L. Poliani, Rosa Maria Moresco, Annapaola Andolfo, Rossella Galli
Journal: Cancer Research (2022)

Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome, and the glycoproteome of human subgroup-specific GBM sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated that most MES-restricted core-fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion, and integrin-mediated signaling. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.
Association of Prenatal Exposure to Benzodiazepines With Development of Autism Spectrum and Attention-Deficit/Hyperactivity Disorders
Authors: Vincent Chin-Hung Chen, Shu-I Wu, Chiao-Fan Lin, Mong-Liang Lu, Yi-Lung Chen, Robert Stewart
Journal: JAMA Network Open (2022)

Importance Prenatal exposure to benzodiazepines is reported to be associated with neurodevelopmental disorders among children, but associations of maternal genetic confounding with neurodevelopmental disorders among children have not been taken into consideration. Objective To ascertain whether prenatal benzodiazepine exposure was associated with development of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Design, Setting, and Participants This cohort study used linked data from birth certificate registration and the Taiwan National Health Insurance Research Database from January 1, 2004, to December 31, 2017, on 1 138 732 mothers with 1 516 846 live births between January 1, 2004, and December 31, 2017. Data were analyzed between February 20, 2021, and September 19, 2022. Exposure Benzodiazepine exposure during pregnancy (first trimester to third trimester) was defined as having at least one benzodiazepine prescription dispensed. Main Outcomes and Measures The main outcomes were ADHD and ASD. Results There were 1 516 846 children (mean [SD] gestational age, 38.5 [1.8] years; 789 455 boys [52.0%]) born full term who were younger than 14 years of age and followed up to 2017; 5.0% of the children (n = 76 411) were exposed to a benzodiazepine during pregnancy. Benzodiazepine exposure during pregnancy was associated with increased risks of ADHD (first trimester exposure: hazard ratio [HR], 1.24 [95% CI, 1.20-1.28]; second trimester exposure: HR, 1.27 [95% CI, 1.21-1.34]; third trimester exposure: HR, 1.25 [95% CI, 1.14-1.37]) and ASD (first trimester exposure: HR, 1.13 [95% CI, 1.05-1.21]; second trimester exposure: HR, 1.10 [95% CI, 0.98-1.22]; third trimester exposure: HR, 1.21 [95% CI, 1.00-1.47]). However, no differences were found with unexposed sibling controls during the same time frame for ADHD (first trimester exposure: HR, 0.91 [95% CI, 0.83-1.00]; second trimester exposure: HR, 0.89 [95% CI, 0.78-1.01]; third trimester exposure: HR, 1.08 [95% CI, 0.83-1.41]) or ASD (first trimester exposure: HR, 0.92 [95% CI, 0.75-1.14]; second trimester exposure: HR, 0.97 [95% CI, 0.71-1.33]; third trimester exposure: HR, 1.07 [95% CI, 0.53-2.16]). Similar findings were also noted in the stratification analysis of short-acting and long-acting benzodiazepines. Conclusions and Relevance This cohort study suggests that previously described adverse neurodevelopmental outcomes associated with benzodiazepine exposure during pregnancy were likely to be accounted for by maternal genetic confounding.
Return on Investment of the COVID-19 Vaccination Campaign in New York City
Authors: Pratha Sah, Thomas N. Vilches, Seyed M. Moghadas, Abhishek Pandey, Suhas Gondi, Eric C. Schneider, Jesse Singer, Dave A. Chokshi, Alison P. Galvani
Journal: JAMA Network Open (2022)

Importance New York City, an early epicenter of the pandemic, invested heavily in its COVID-19 vaccination campaign to mitigate the burden of disease outbreaks. Understanding the return on investment (ROI) of this campaign would provide insights into vaccination programs to curb future COVID-19 outbreaks. Objective To estimate the ROI of the New York City COVID-19 vaccination campaign by estimating the tangible direct and indirect costs from a societal perspective. Design, Setting, and Participants This decision analytical model of disease transmission was calibrated to confirmed and probable cases of COVID-19 in New York City between December 14, 2020, and January 31, 2022. This simulation model was validated with observed patterns of reported hospitalizations and deaths during the same period. Exposures An agent-based counterfactual scenario without vaccination was simulated using the calibrated model. Main Outcomes and Measures Costs of health care and deaths were estimated in the actual pandemic trajectory with vaccination and in the counterfactual scenario without vaccination. The savings achieved by vaccination, which were associated with fewer outpatient visits, emergency department visits, emergency medical services, hospitalizations, and intensive care unit admissions, were also estimated. The value of a statistical life (VSL) lost due to COVID-19 death and the productivity loss from illness were accounted for in calculating the ROI. Results During the study period, the vaccination campaign averted an estimated $27.96 (95% credible interval [CrI], $26.19-$29.84) billion in health care expenditures and 315 724 (95% CrI, 292 143-340 420) potential years of life lost, averting VSL loss of $26.27 (95% CrI, $24.39-$28.21) billion. The estimated net savings attributable to vaccination were $51.77 (95% CrI, $48.50-$55.85) billion. Every $1 invested in vaccination yielded estimated savings of $10.19 (95% CrI, $9.39-$10.87) in direct and indirect costs of health outcomes that would have been incurred without vaccination. Conclusions and Relevance Results of this modeling study showed an association of the New York City COVID-19 vaccination campaign with reduction in severe outcomes and avoidance of substantial economic losses. This significant ROI supports continued investment in improving vaccine uptake during the ongoing pandemic.
Phase IIb Randomized, Placebo-Controlled, Dose-Escalating, Double-Blind Study of Cannabidiol Oil for the Relief of Symptoms in Advanced Cancer (MedCan1-CBD)
Authors: Janet Hardy, Ristan Greer, Georgie Huggett, Alison Kearney, Taylan Gurgenci, Phillip Good
Journal: Journal of Clinical Oncology (2022)

To determine whether cannabidiol (CBD) oil can improve symptom distress in patients with advanced cancer receiving palliative care.Participants were adults with advanced cancer and symptom distress (Edmonton Symptom Assessment Scale [ESAS] total score of ≥ 10/90) who received titrated CBD oil 100 mg/mL, 0.5 mL once daily to 2 mL three times a day, or matched placebo for 28 days. The primary outcome was ESAS total symptom distress score (TSDS) at day 14. Response was defined as a decrease in TSDS by ≥ 6 at day 14. Secondary outcomes were ESAS TSDS over time, individual symptom scores, patient-determined effective dose, opioid use, Global Impression of Change, depression, anxiety, quality of life, and adverse events.Of the 144 patients randomly assigned, the planned sample size of 58 participants on CBD and 63 on placebo reached the primary analysis point (day 14). The unadjusted change in TSDS from baseline to day 14 was -6.2 (standard deviation, 14.5) for placebo and -3.0 (standard deviation, 15.2) for CBD with no significant difference between arms (P = .24). Similarly, there was no detected difference in proportion of responders (placebo: 37 of 63 [58.7%], CBD: 26 of 58 [44.8%], P = .13). All components of ESAS improved (fell) over time with no difference between arms. The median dose of participant-selected CBD was 400 mg per day with no correlation with opioid dose. There was no detectable effect of CBD on quality of life, depression, or anxiety. Adverse events did not differ significantly between arms apart from dyspnea that was more common with CBD. Most participants reported feeling better or much better at days 14 (53% CBD and 65% placebo) and 28 (70% CBD and 64% placebo).CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.
GAO Calls for Nationwide Analysis of “Forever Chemicals”
Authors: Melissa Suran
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal